Molecular Autism (Aug 2021)

The Monash Autism-ADHD genetics and neurodevelopment (MAGNET) project design and methodologies: a dimensional approach to understanding neurobiological and genetic aetiology

  • Rachael Knott,
  • Beth P. Johnson,
  • Jeggan Tiego,
  • Olivia Mellahn,
  • Amy Finlay,
  • Kathryn Kallady,
  • Maria Kouspos,
  • Vishnu Priya Mohanakumar Sindhu,
  • Ziarih Hawi,
  • Aurina Arnatkeviciute,
  • Tracey Chau,
  • Dalia Maron,
  • Emily-Clare Mercieca,
  • Kirsten Furley,
  • Katrina Harris,
  • Katrina Williams,
  • Alexandra Ure,
  • Alex Fornito,
  • Kylie Gray,
  • David Coghill,
  • Ann Nicholson,
  • Dinh Phung,
  • Eva Loth,
  • Luke Mason,
  • Declan Murphy,
  • Jan Buitelaar,
  • Mark A. Bellgrove

DOI
https://doi.org/10.1186/s13229-021-00457-3
Journal volume & issue
Vol. 12, no. 1
pp. 1 – 24

Abstract

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Abstract Background ASD and ADHD are prevalent neurodevelopmental disorders that frequently co-occur and have strong evidence for a degree of shared genetic aetiology. Behavioural and neurocognitive heterogeneity in ASD and ADHD has hampered attempts to map the underlying genetics and neurobiology, predict intervention response, and improve diagnostic accuracy. Moving away from categorical conceptualisations of psychopathology to a dimensional approach is anticipated to facilitate discovery of data-driven clusters and enhance our understanding of the neurobiological and genetic aetiology of these conditions. The Monash Autism-ADHD genetics and neurodevelopment (MAGNET) project is one of the first large-scale, family-based studies to take a truly transdiagnostic approach to ASD and ADHD. Using a comprehensive phenotyping protocol capturing dimensional traits central to ASD and ADHD, the MAGNET project aims to identify data-driven clusters across ADHD-ASD spectra using deep phenotyping of symptoms and behaviours; investigate the degree of familiality for different dimensional ASD-ADHD phenotypes and clusters; and map the neurocognitive, brain imaging, and genetic correlates of these data-driven symptom-based clusters. Methods The MAGNET project will recruit 1,200 families with children who are either typically developing, or who display elevated ASD, ADHD, or ASD-ADHD traits, in addition to affected and unaffected biological siblings of probands, and parents. All children will be comprehensively phenotyped for behavioural symptoms, comorbidities, neurocognitive and neuroimaging traits and genetics. Conclusion The MAGNET project will be the first large-scale family study to take a transdiagnostic approach to ASD-ADHD, utilising deep phenotyping across behavioural, neurocognitive, brain imaging and genetic measures.

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